Sindbis virus will be employed as a model insect vectored virus in studies investigating the interaction of these agents with the invertebrate hosts. The development of Sindbis virus in tissue cultured mosquito cells will be studied in an attempt to learn how this virus is able to establish a persistent state of infection in these cells without the gross cytopathic effect and cell death that occurs in cultured vertebrate cells. The morphological, genetic and biochemical-molecular biological events occurring in the invertebrate cells will be determined and compared to analogous processes in cultured vertebrate cells. Particular attention will be given to the structure and function of a non-interferon antiviral compound produced specifically by the infected mosquito cell which inhibits the growth of the infecting virus. We have recently developed procedures for the production of insect-vertebrate cell hybrids which can be passaged in cell culture. The pattern of Sindbis virus development in these hybrids will be examined to determine which phenotypic responses to alphavirus infection are dominant. Attempts will be made to correlate specific responses (such as ability to form persistent infections or production of antiviral compound) with a particular insect chromosome. Arthropod vectored virus induced diseases of man and domestic animals are in resurgence in the United States. Tissue cultured arthropod cells are under consideration as a substitute for the production of vaccines. The information obtained from this study will prove important in understanding the virus insect cell relationship and establishment of non-toxic infection leading to transovarial transmission of insect viruses. Such information will prove important in controlling the spread of these viruses in nature and the disease process in man.